Lung cancer is the most prevalent cancer worldwide and responsible for the most cancer deaths in the United States. Existing therapies include surgery, radiation, or chemotherapy to kill the tumor cells, but these options are not adequate for the vast majority of patients. Thus, there is a significant need to develop new therapeutic approaches. One of the most promising areas of development is immunotherapy, which reprograms the immune system to recognize and eliminate the tumor. We identified a protein that is expressed on lung cancer cells that may allow a tumor to evade the immune system by regulating the recruitment of host immune cells. Our goal is to develop a neutralizing antibody that will inhibit the activity of this protein and reactivate the anti- tumor immune response, resulting in tumor regression. We have produced monoclonal antibodies against this target. This first aim of this proposal is to characterize the antibodies in molecular and cellular assays to select the optimal antibody based upon binding the target and inhibiting its signaling activity. The second aim of the proposal will test the antibody in mouse tumor models and determine if the antibody inhibits tumor growth. This proposal is the foundation for development of an antibody for use as human therapeutics. If successful, it will result in a new treatment option tha will improve survival for patients with lung cancer.